Adolescence is a complex transitional period in human development, composing physical maturation, cognitive and social behavioral changes. The objective of this study is to investigate sex differences in white matter development and the associations between intelligence and white matter microstructure in the adolescent brain using diffusion tensor imaging (DTI) and tract-based spatial statistics (TBSS). In a cohort of 16 typically-developing adolescents aged 13 to 17 years, longitudinal DTI data were recorded from each subject at two time points that were one year apart. We used TBSS to analyze the diffusion indices including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD). Our results suggest that boys (13–18 years) continued to demonstrate white matter maturation, whereas girls appeared to reach mature levels earlier. In addition, we identified significant positive correlations between FA and full-scale intelligence quotient (IQ) in the right inferior fronto-occipital fasciculus when both sexes were looked at together. Only girls showed significant positive correlations between FA and verbal IQ in the left cortico-spinal tract and superior longitudinal fasciculus. The preliminary evidence presented in this study supports that boys and girls have different developmental trajectories in white matter microstructure.

This fMRI study investigated the development of language lateralization in left- and right-handed children between 5 and 18 years of age. Twenty-seven left-handed children (17 boys, 10 girls) and 54 age- and gender-matched right-handed children were included. We used functional MRI at 3T and a verb generation task to measure hemispheric language dominance based on either frontal or temporo-parietal regions of interest (ROIs) defined for the entire group and applied on an individual basis. Based on the frontal ROI, in the left-handed group, 23 participants (85%) demonstrated left-hemispheric language lateralization, 3 (11%) demonstrated symmetric activation, and 1 (4%) demonstrated right-hemispheric lateralization. In contrast, 50 (93%) of the right-handed children showed left-hemisphere lateralization and 3 (6%) demonstrated a symmetric activation pattern, while one (2%) demonstrated a right- hemisphere lateralization. The corresponding values for the temporo-parietal ROI for the left-handed children were 18 (67%) left-dominant, 6 (22%) symmetric, 3 (11%) right-dominant and for the right-handed children 49 (91%), 4 (7%), 1 (2%). Left-hemispheric language lateralization increased with age in both groups but somewhat different lateralization trajectories were observed in girls when compared to boys. The incidence of atypical language lateralization in left-handed children in this study was similar to that reported in adults. We also found similar rates of increase in left-hemispheric language lateralization with age between groups (i.e., independent of handedness) indicating the presence of similar mechanisms for language lateralization in left- and right-handed children.

Comprehension of spoken narratives requires coordination of multiple language skills. As such, for normal children narrative skills develop well into the school years and, during this period, are particularly vulnerable in the face of brain injury or developmental disorder. For these reasons, we sought to determine the developmental trajectory of narrative processing using longitudinal fMRI scanning. 30 healthy children between the ages of 5 and 18 enrolled at ages 5, 6, or 7, were examined annually for up to 10 years. At each fMRI session, children were presented with a set of five, 30s–long, stories containing 9, 10, or 11 sentences designed to be understood by a 5 year old child. FMRI data analysis was conducted based on a hierarchical linear model (HLM) that was modified to investigate developmental changes while accounting for missing data and controlling for factors such as age, linguistic performance and IQ. Performance testing conducted after each scan indicated well above the chance (p < 0.002) comprehension performance. There was a linear increase with increasing age in bilateral superior temporal cortical activation (BA 21 and 22) linked to narrative processing. Conversely, age-related decreases in cortical activation were observed in bilateral occipital regions, cingulate and cuneus, possibly reflecting changes in the default mode networks. The dynamic changes observed in this longitudinal fMRI study support the increasing role of bilateral BAs 21 and 22 in narrative comprehension, involving non-domain-specific integration in order to achieve final story interpretation. The presence of a continued linear development of this area throughout childhood and teenage years with no apparent plateau, indicates that full maturation of narrative processing skills has not yet occurred and that it may be delayed to early adulthood.

Background and Purpose White matter structural alterations and the correlation with neuropsychological deficits in children with hydrocephalus have not been well investigated. In this prospective study, the objectives were to: (1) apply DTI to detect in vivo white matter alterations based on diffusion properties in children with acute hydrocephalus; (2) quantify early neuropsychological deficits; and (3) explore the correlation between potential neuropsychological deficits and abnormalities in functionally related white matter. Methods A total of 44 children, 24 with hydrocephalus and 20 controls, were enrolled in the study. DTI indices, FA, MD, AD, RD were evaluated in the gCC, sCC, PLIC, and ALIC. The ABAS-II was used as a broad screener of development, including conceptual, social, practical and motor skills. The correlation between the Motor scale and DTI indices in the PLIC was analyzed. Results DTI analyses showed that the gCC and sCC in children with hydrocephalus had lower FA and higher MD driven by the increased RD with statistical significance (p<0.05) or trend level significance (p=0.06). The PLIC and ALIC had significantly higher AD in children with hydrocephalus (p<0.05). On the ABAS-II, parent ratings of general adaptive skills, conceptual skills and motor skills were significantly lower in children with hydrocephalus (all at p level <0.05). The MD and RD value in the PLIC were found to have trend level or significant correlation with the Motor scale (p=0.057, 0.041, respectively). Conclusions DTI reveals alterations in white matter structure in children with hydrocephalus with preliminary findings suggesting correlation with clinical motor deficits.

OBJECTIVE The purpose of this study was to investigate white matter (WM) structural abnormalities using diffusion tensor imaging (DTI) in children with hydrocephalus before CSF diversionary surgery (including ventriculoperitoneal shunt insertion and endoscopic third ventriculostomy) and during the course of recovery after surgery in association with neuropsychological and behavioral outcome. METHODS This prospective study included 54 pediatric patients with congenital hydrocephalus (21 female, 33 male; age range 0.03–194.5 months) who underwent surgery and 64 normal controls (30 female, 34 male; age range 0.30–197.75 months). DTI and neurodevelopmental outcome data were collected once in the control group and 3 times (preoperatively and at 3 and 12 months postoperatively) in the patients with hydrocephalus. DTI measures, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) values were extracted from the genu of the corpus callosum (gCC) and the posterior limb of internal capsule (PLIC). Group analysis was performed first cross-sectionally to quantify DTI abnormalities at 3 time points by comparing the data obtained in the hydrocephalus group for each of the 3 time points to data obtained in the controls. Longitudinal comparisons were conducted pairwise between different time points in patients whose data were acquired at multiple time points. Neurodevelopmental data were collected and analyzed using the Adaptive Behavior Assessment System, Second Edition, and the Bayley Scales of Infant Development, Third Edition. Correlation analyses were performed between DTI and behavioral measures. RESULTS Significant DTI abnormalities were found in the hydrocephalus patients in both the gCC (lower FA and higher MD, AD, and RD) and the PLIC (higher FA, lower AD and RD) before surgery. The DTI measures in the gCC remained mostly abnormal at 3 and 12 months after surgery. The DTI abnormalities in the PLIC were significant in FA and AD at 3 months after surgery but did not persist when tested at 12 months after surgery. Significant longitudinal DTI changes in the patients with hydrocephalus were found in the gCC when findings at 3 and 12 months after surgery were compared. In the PLIC, trend-level longitudinal changes were observed between preoperative findings and 3-month postoperative findings, as well as between 3- and 12-month postoperative findings. Significant correlation between DTI and developmental outcome was found at all 3 time points. Notably, a significant correlation was found between DTI in the PLIC at 3 months after surgery and developmental outcome at 12 months after surgery. CONCLUSIONS The data showed significant WM abnormality based on DTI in both the gCC and the PLIC in patients with congenital hydrocephalus before surgery, and the abnormalities persisted in both the gCC and the PLIC at 3 months after surgery. The DTI values remained significantly abnormal in the gCC at 12 months after surgery. Longitudinal analysis showed signs of recovery in both WM structures between different time points. Combined with the significant correlation found between DTI and neuropsychological measures, the findings of this study suggest that DTI can serve as a sensitive imaging biomarker for underlying neuroanatomical changes and postsurgical developmental outcome and even as a predictor for future outcomes.